This shared instrumentation grant application is to acquire a state-of-the-art confocal microscopy imaging system (Zeiss LSM 510 core unit + critical upgrades) to replace our aging, limited-capability system (Nikon PCM 2000) and allow our user base to expand into critical and novel applications/techniques. Our present user base of 19 NIH-funded investigators with qualifying grants is comprised of faculty from several departments in the Schools of Medicine (Medicine, Pathology, Physiology and Biophysics, Biochemistry), Pharmaceutical Sciences and Dentistry. They have been using our existing system housed in the Confocal Microscopy Subcore of the Cell Biology Core of USC's Research Center for Liver Diseases (RCLD). This facility has been the sole and/or primary confocal microscopy resource they have access to. Although Nikon PCM 2000 is a workhorse instrument, it is capable of only simple 2-color imaging in fixed specimens and lacks advanced capabilities, such as live cell and time-lapse imaging, imaging specimens labeled with 3 or 4 fluorophores, fluorescence recovery after photobleaching, or fluorescence resonance energy transfer, which are sorely needed by our user base. The other four existing system on our campus are either dedicated to special uses or overloaded with their own user base. The new system will replace our old and be housed-operated in the same facility, with space/darkroom in place. RCLD is funded by NIH P30 DK 48522, Dr. Neil Kaplowitz, P.I., which is in its 3rd 5-yr cycle (3/1/05-2/28/10). It has an established track record in terms of all the necessary infrastructure, administrative, technical (full-time microscopy specialist) and financial (budget for warranty service-maintenance of microscope), to maintain and operate the new equipment. Drs. Murad Ookhtens and Sarah Hamm-Alvarez, the P.I. and co-P.I. on this application, serve as co-directors of the Cell Biology Core, a subcore of which houses the confocal microscopy equipment. They are highly experienced investigators, with extensive cumulative record and expertise in overseeing the use of a large base of sophisticated instrumentation and will share in technical oversight and management of the use of the new system, as they have done with the old. Relevance: The equipment will substantially advance the research of faculty involved in studying the normal and diseased states of the liver (hepatitis C, alcoholic/drug toxicity and injury), heart, lung, kidney, eye, teeth, as well as investigating various methods of drug delivery. [unreadable] [unreadable] [unreadable]